Plant RNAs Found in Mammals

MicroRNAs from plants accumulate in mammalian blood and tissues, where they can regulate gene expression.

By Cristina Luiggi | September 20, 2011

DREAMSTIME.COM, REWAT WANNASUK

MicroRNAs from common plant crops such as rice and cabbage can be found in the blood and tissues of humans and other plant-eating mammals, according to a study published today in Cell Research. One microRNA in particular, MIR168a, which is highly enriched in rice, was found to inhibit a protein that helps removes low-density lipoprotein (LDL) from the blood, suggesting that microRNAs can influence gene expression across kingdoms.

“This is a very exciting piece of work that suggests that the food we eat may directly regulate gene expression in our bodies,” said Clay Marsh, Director of the Center for Personalized Health Care at the Ohio State University College of Medicine who researches microRNA expression in human blood but who was not involved in the study.

MicroRNAs are, as the name implies, very short RNA sequences (approximately 22 nucleotides in length) discovered in the early 1990s. They are known to modulate gene expression by binding to mRNA, often resulting in inhibition. With the recent discovery that microRNAs circulate the blood by hitching a ride in small membrane-encased particles known as microvesicles (see our July 2011 feature on microvesicles, “Exosome Explosion”), there has been a surge of interest in microRNAs as a novel class of biomarkers for a variety of diseases.

Chen-Yu Zhang, a molecular biologist at Nanjing University in China, was studying the role of circulating microRNAs in health and disease when he discovered that microRNAs are present in other bodily fluids such as milk. This gave him the “crazy idea” that exogenous microRNAs, such as those ingested through the consumption of milk, could also be found circulating in the serum of mammals, he recalled.

To test his hypothesis, Zhang and his team of researchers sequenced the blood microRNAs of 31 healthy Chinese subjects and searched for the presence of plant microRNAs. Because plant microRNAs are structurally different from those of mammals, they react differently to oxidizing agents, and the researchers were able to differentiate the two by treating them with sodium periodate, which oxidizes mammal but not plant microRNAs.

To their surprise, they found about 40 types of plant microRNAs circulating in the subjects’ blood—some of which were found in concentrations that were comparable to major endogenous human microRNAs.

The plant microRNAs with the highest concentrations were MIR156a and MIR168a, both of which are known to be enriched in rice and cruciferous vegetables such as cauliflower, cabbage, and broccoli. Furthermore, the researchers detected the two microRNAs in the blood, lungs, small intestine, and livers of mice, in variable concentrations that significantly increased after the mice were fed raw rice (although cooked rice was also shown to contain intact MIR168a).

Next, the researchers scoured sequence databases for putative target genes of MIR156a and MIR168a and found that MIR168a shared sequence complementarity with approximately 50 mammalian genes. The most highly conserved of these sequences across the animal kingdom was the exon 4 of the low-density lipoprotein receptor adapter protein 1 gene (LDLRAP1).

LDLRAP1 is highly expressed in the liver, where it interacts with the low-density lipoprotein receptor to help remove low-density lipoprotein (LDL), aka “bad” cholesterol, from the blood.

The researchers hypothesized that MIR168a could be taken up by the epithelial cells lining the gastrointestinal tract, packaged into microvesicles, and secreted into the blood stream, where they can make their way to target organs. Once in the liver, MIR168a binds to LDLRAP1 mRNA, reducing the protein levels and ultimately impairing the removal of LDL from the blood.

To test this hypothesis in vitro, the researchers transfected synthetic MIR168a into a human epithelial cell line and collected the secreted microvesicles. When they added these microvesicles to a liver cell line called HepG2, they found that while it did not change the levels of LDLRAP1 mRNA, it did decrease the levels of the actual LDLRAP1 protein.

Likewise, the LDLRAP1 protein level decreased in the livers of live mice 3 to 7 days after eating fresh rice or being injected with synthetic MIR168a—significantly increasing LDL in the blood. When the researchers injected the mice with an RNA sequence that bound to and neutralized MIR168a, the protein and LDL levels returned to normal.

“This microRNA inhibits this protein and increased the plasma LDL levels,” Zhang said. With higher levels of circulating cholesterol, “it can possibly increase the risk of metabolic syndrome,” he added. But more importantly, this research points to a “new therapeutic strategy for the treatment of diseases,” based on the enhancement or inhibition of exogenous microRNAs.

Although the team has still a long way to go in elucidating the mechanisms by which plant microRNAs can regulate gene expression in humans, these initial results promise to increase the understanding of how specific ingredients in food can mediate health and disease, Marsh said.

Indeed, Zhang suspects that this is just one example of many. With time, “I’m confident other people will find more exogenous plant microRNAs that can pass through the GI tract and also have effects on the host physiology,” Zhang said.

This finding suggests that we need to be very careful in spreading transgenic crops when their safety has not yet fully tested.Â As a matter of fact, this study has demonstrated a need for expanding the scope of food safety detection measures.

Why is any risk associated with this phenomena greater with transgenic plants than varieties produced via plant breeding?Â Traditional breeding, especially to distantly related wild relatives, is more likely to alter microRNA profiles in plants than is the insertion of a single recombinant gene.

This opens up new avenues of research in understanding the historical record of food remedies â€“ ancient to modern. Similarly in expands the possibilities of understanding nutritional strategies to treat diseases â€“ beyond the existing vitamin knowledge-base. Many inflammatory and auto-immune diseases are not understood â€“ but clearly have relationships to food. Finally, other modern research suggests that pharmaceuticals work differentially in different people. I was involved in research that suggested that our pharmaceutical worked much better in fish eaters than in heavy beef eaters (viz never experimentally confirmed).

If you make it vague enough you can claim that it validates any pseudoscience of your liking. Just out of curiosity, how does the periodic table validates the Ayurvedic notion that there only exist five elements? Maybe if only count until boron...

This important finding in mammals ispredicted by an insect model in which the diet of the honeybee queen and herpheromones determine everything about the success of the hive including theneuroanatomy of worker bee brains.

Thehoneybee already serves as a model organism for studying human immunity,disease resistance, allergic reaction, circadian rhythms, antibioticresistance, development, mental health, longevity, and diseases of the Xchromosome. Included among these different aspects of eusocial species survivalare learning and memory as well as conditioned responses to sensory stimuli,like food odors, and the social odors called pheromones. Thus, thehoneybee model also predicts that the behavior of mammals will be influenced byfood odors, nutrition, and pheromones to the same degree that chemical stimuliinfluence the behavior of every other species on the planet.

In mammals, of course, theepigenetic effects of pheromones in the mother's milk are clearer, perhaps even to non-biologists.

If you really want to start a controversy, one could say that this may validate the Bibleâ€™s inference that longevity can be connected to a â€œtree of life.â€쳌Â Â I am sure that someone will make the connection and open up a whole line of research connected to discovering how what we eat can extend our age.

This is an important enough and unexpected enough finding that we should not accept it at face value until it has been confirmed in different (independent) laboratories.Â Oatmeal has been alleged to decrease LDL levels.Â I wonder if (assumingÂ the allegations about oatmeal and microRNAs are bothÂ correct in the first place) thisÂ mightÂ also be via some microRNA mechanism.

For me, it means I should eat more chocolate before prices skyrocket -- they will either demonstrate its health benefits (driving up demand), or find there is something unhealthful it (increasing its cost due to increased regulation).Â

One might point out you use the word "nutritional" in your question.Â Blah, blah, blah...

This finding suggests that we need to be very careful in spreading transgenic crops when their safety has not yet fully tested.Â As a matter of fact, this study has demonstrated a need for expanding the scope of food safety detection measures.

This important finding in mammals ispredicted by an insect model in which the diet of the honeybee queen and herpheromones determine everything about the success of the hive including theneuroanatomy of worker bee brains.

Thehoneybee already serves as a model organism for studying human immunity,disease resistance, allergic reaction, circadian rhythms, antibioticresistance, development, mental health, longevity, and diseases of the Xchromosome. Included among these different aspects of eusocial species survivalare learning and memory as well as conditioned responses to sensory stimuli,like food odors, and the social odors called pheromones. Thus, thehoneybee model also predicts that the behavior of mammals will be influenced byfood odors, nutrition, and pheromones to the same degree that chemical stimuliinfluence the behavior of every other species on the planet.

In mammals, of course, theepigenetic effects of pheromones in the mother's milk are clearer, perhaps even to non-biologists.

Why is any risk associated with this phenomena greater with transgenic plants than varieties produced via plant breeding?Â Traditional breeding, especially to distantly related wild relatives, is more likely to alter microRNA profiles in plants than is the insertion of a single recombinant gene.

If you really want to start a controversy, one could say that this may validate the Bibleâ€™s inference that longevity can be connected to a â€œtree of life.â€쳌Â Â I am sure that someone will make the connection and open up a whole line of research connected to discovering how what we eat can extend our age.

This important finding in mammals ispredicted by an insect model in which the diet of the honeybee queen and herpheromones determine everything about the success of the hive including theneuroanatomy of worker bee brains.

Thehoneybee already serves as a model organism for studying human immunity,disease resistance, allergic reaction, circadian rhythms, antibioticresistance, development, mental health, longevity, and diseases of the Xchromosome. Included among these different aspects of eusocial species survivalare learning and memory as well as conditioned responses to sensory stimuli,like food odors, and the social odors called pheromones. Thus, thehoneybee model also predicts that the behavior of mammals will be influenced byfood odors, nutrition, and pheromones to the same degree that chemical stimuliinfluence the behavior of every other species on the planet.

In mammals, of course, theepigenetic effects of pheromones in the mother's milk are clearer, perhaps even to non-biologists.

This is an important enough and unexpected enough finding that we should not accept it at face value until it has been confirmed in different (independent) laboratories.Â Oatmeal has been alleged to decrease LDL levels.Â I wonder if (assumingÂ the allegations about oatmeal and microRNAs are bothÂ correct in the first place) thisÂ mightÂ also be via some microRNA mechanism.

If you really want to start a controversy, one could say that this may validate the Bibleâ€™s inference that longevity can be connected to a â€œtree of life.â€쳌Â Â I am sure that someone will make the connection and open up a whole line of research connected to discovering how what we eat can extend our age.

This is an important enough and unexpected enough finding that we should not accept it at face value until it has been confirmed in different (independent) laboratories.Â Oatmeal has been alleged to decrease LDL levels.Â I wonder if (assumingÂ the allegations about oatmeal and microRNAs are bothÂ correct in the first place) thisÂ mightÂ also be via some microRNA mechanism.

This opens up new avenues of research in understanding the historical record of food remedies â€“ ancient to modern. Similarly in expands the possibilities of understanding nutritional strategies to treat diseases â€“ beyond the existing vitamin knowledge-base. Many inflammatory and auto-immune diseases are not understood â€“ but clearly have relationships to food. Finally, other modern research suggests that pharmaceuticals work differentially in different people. I was involved in research that suggested that our pharmaceutical worked much better in fish eaters than in heavy beef eaters (viz never experimentally confirmed).

If you make it vague enough you can claim that it validates any pseudoscience of your liking. Just out of curiosity, how does the periodic table validates the Ayurvedic notion that there only exist five elements? Maybe if only count until boron...

This opens up new avenues of research in understanding the historical record of food remedies â€“ ancient to modern. Similarly in expands the possibilities of understanding nutritional strategies to treat diseases â€“ beyond the existing vitamin knowledge-base. Many inflammatory and auto-immune diseases are not understood â€“ but clearly have relationships to food. Finally, other modern research suggests that pharmaceuticals work differentially in different people. I was involved in research that suggested that our pharmaceutical worked much better in fish eaters than in heavy beef eaters (viz never experimentally confirmed).

For me, it means I should eat more chocolate before prices skyrocket -- they will either demonstrate its health benefits (driving up demand), or find there is something unhealthful it (increasing its cost due to increased regulation).Â

One might point out you use the word "nutritional" in your question.Â Blah, blah, blah...

If you make it vague enough you can claim that it validates any pseudoscience of your liking. Just out of curiosity, how does the periodic table validates the Ayurvedic notion that there only exist five elements? Maybe if only count until boron...

This finding suggests that we need to be very careful in spreading transgenic crops when their safety has not yet fully tested.Â As a matter of fact, this study has demonstrated a need for expanding the scope of food safety detection measures.

Why is any risk associated with this phenomena greater with transgenic plants than varieties produced via plant breeding?Â Traditional breeding, especially to distantly related wild relatives, is more likely to alter microRNA profiles in plants than is the insertion of a single recombinant gene.

For me, it means I should eat more chocolate before prices skyrocket -- they will either demonstrate its health benefits (driving up demand), or find there is something unhealthful it (increasing its cost due to increased regulation).Â

One might point out you use the word "nutritional" in your question.Â Blah, blah, blah...

That's a false statement -- the issue of feeding the world's population is an issue of logistics and finance - not of capacity. The globe produces enough calorific matter to feed twice the population we have today. The western world places a third of the food supply into landfill alone. Personally, I welcome GMOs as a valid and pertinent technology. I think it is often misused to create profit centric crops rather than solve actual food issues, but that is a fault of failed regulators and governments who do not support research in the academics and public domain. The point being this: do not believe that any one thing - in this case GMO - will be a magic bullet for any problem and do challenge the accepted status quo to demand better.

Returning to your original statement though, we are far better served by the development of faster and cheaper transport than the GM modified crops in solving world population feeding.

Of course the food we eat influences many processes in our bodies, including gene expression - think of zinc needed in zinc-finger domain containing transcription factors. RNA from our food in that role is highly unlikely though. Every RNA handling researcher knows that it is already broken down 'by just looking at it'. RNases are everywhere. You would need tons of it for survival of a tiny bit in the tractus digestivus. The uptake (it is highly charged) would be almost impossible, and survival in the bloodstream even more unlikely than in the intestine. Uptake by individual cells is equally difficult. If genetic material from the gut could reach our cells that easily, we, no life,Â would have become extinct a very long time ago. In fact, it might never have started.

Natural crops are in fact already full of molecules which interact with our metabolism. Adding a resistance gene which is encoding a protein only active against insects will not change this.Anyway feeding 7 000 000 000 humans with organic crops is impossible.And we'll be 10 000 000 000 soon...

Natural crops are in fact already full of molecules which interact with our metabolism. Adding a resistance gene which is encoding a protein only active against insects will not change this.Anyway feeding 7 000 000 000 humans with organic crops is impossible.And we'll be 10 000 000 000 soon...

Thank youÂ Shi V. Liu for your comments.Â Right on.Â I might add that genetic crops and processed foods, herbicides,Â insecticides, etc.Â make for a very toxic soup all around. You will become what you eat - poisoned beyond DNA repair. This study is headed in the right direction.

Of course the food we eat influences many processes in our bodies, including gene expression - think of zinc needed in zinc-finger domain containing transcription factors. RNA from our food in that role is highly unlikely though. Every RNA handling researcher knows that it is already broken down 'by just looking at it'. RNases are everywhere. You would need tons of it for survival of a tiny bit in the tractus digestivus. The uptake (it is highly charged) would be almost impossible, and survival in the bloodstream even more unlikely than in the intestine. Uptake by individual cells is equally difficult. If genetic material from the gut could reach our cells that easily, we, no life,Â would have become extinct a very long time ago. In fact, it might never have started.

Thank youÂ Shi V. Liu for your comments.Â Right on.Â I might add that genetic crops and processed foods, herbicides,Â insecticides, etc.Â make for a very toxic soup all around. You will become what you eat - poisoned beyond DNA repair. This study is headed in the right direction.

This article gives clue and make us aware about what we eat can also have a impact on gene regulation and expression. The role of plant microRNA present in rice in controlling levels of LDL is noteworthy.

This article gives clue and make us aware about what we eat can also have a impact on gene regulation and expression. The role of plant microRNA present in rice in controlling levels of LDL is noteworthy.

Diseases that have both an environmental and genetic component, such as autism, could be explained by this mechanism of foreign micro RNA. Very interesting to see if experiments find high levels of certain kinds of foreign regulatory RNA in such patients.

Diseases that have both an environmental and genetic component, such as autism, could be explained by this mechanism of foreign micro RNA. Very interesting to see if experiments find high levels of certain kinds of foreign regulatory RNA in such patients.

That's a false statement -- the issue of feeding the world's population is an issue of logistics and finance - not of capacity. The globe produces enough calorific matter to feed twice the population we have today. The western world places a third of the food supply into landfill alone. Personally, I welcome GMOs as a valid and pertinent technology. I think it is often misused to create profit centric crops rather than solve actual food issues, but that is a fault of failed regulators and governments who do not support research in the academics and public domain. The point being this: do not believe that any one thing - in this case GMO - will be a magic bullet for any problem and do challenge the accepted status quo to demand better.

Returning to your original statement though, we are far better served by the development of faster and cheaper transport than the GM modified crops in solving world population feeding.

Diseases that have both an environmental and genetic component, such as autism, could be explained by this mechanism of foreign micro RNA. Very interesting to see if experiments find high levels of certain kinds of foreign regulatory RNA in such patients.

Of course the food we eat influences many processes in our bodies, including gene expression - think of zinc needed in zinc-finger domain containing transcription factors. RNA from our food in that role is highly unlikely though. Every RNA handling researcher knows that it is already broken down 'by just looking at it'. RNases are everywhere. You would need tons of it for survival of a tiny bit in the tractus digestivus. The uptake (it is highly charged) would be almost impossible, and survival in the bloodstream even more unlikely than in the intestine. Uptake by individual cells is equally difficult. If genetic material from the gut could reach our cells that easily, we, no life,Â would have become extinct a very long time ago. In fact, it might never have started.

Natural crops are in fact already full of molecules which interact with our metabolism. Adding a resistance gene which is encoding a protein only active against insects will not change this.Anyway feeding 7 000 000 000 humans with organic crops is impossible.And we'll be 10 000 000 000 soon...

That's a false statement -- the issue of feeding the world's population is an issue of logistics and finance - not of capacity. The globe produces enough calorific matter to feed twice the population we have today. The western world places a third of the food supply into landfill alone. Personally, I welcome GMOs as a valid and pertinent technology. I think it is often misused to create profit centric crops rather than solve actual food issues, but that is a fault of failed regulators and governments who do not support research in the academics and public domain. The point being this: do not believe that any one thing - in this case GMO - will be a magic bullet for any problem and do challenge the accepted status quo to demand better.

Returning to your original statement though, we are far better served by the development of faster and cheaper transport than the GM modified crops in solving world population feeding.

Thank youÂ Shi V. Liu for your comments.Â Right on.Â I might add that genetic crops and processed foods, herbicides,Â insecticides, etc.Â make for a very toxic soup all around. You will become what you eat - poisoned beyond DNA repair. This study is headed in the right direction.

This article gives clue and make us aware about what we eat can also have a impact on gene regulation and expression. The role of plant microRNA present in rice in controlling levels of LDL is noteworthy.

This fascinating news corroborates Pellionisz's Recursive Genome Function, as earlier demonstrated, from the clinical view-point, by well-known Manuel's Story, the first newborn without predisposition to cancer although its mother was positive before therapy.

Agreed. During my life, most things this flabbergasting have turned out to be wrong. Let's see it tested in some lab that does not have miR168 contaminating every surface. If true, it's a game changer for many areas of science and medicine, so I hope it is true. But it seems too dramatically inconsistent with the nature of RNA, 3' methyl or not. Put it to the test.

"Discover how what we eat can extend our age"... can extrapolate toÂ if we don't eat food, we die.Â So the longer we eat, the longer we live.Â I'd like to get that research grant.Â The work of limiting caloric intake and replacing functional calories with non-nutritive calories is currently widespread in the USA, with millions of participants in the study...

Maybe I am missing the Main point of this article BUT, We (humans) share 40%of our D N A with Bananas.TheÂ research associatingÂ the rice gene is negligible compared to what we already KNOW! of ,naturally grown, rice's many positive benefits . P S daruma doll is a Monsanto Hugging SuitÂ exposed by Â Tree Hugger xntrek.Â thanksÂ man!!

Maybe I am missing the Main point of this article BUT, We (humans) share 40%of our D N A with Bananas.TheÂ research associatingÂ the rice gene is negligible compared to what we already KNOW! of ,naturally grown, rice's many positive benefits . P S daruma doll is a Monsanto Hugging SuitÂ exposed by Â Tree Hugger xntrek.Â thanksÂ man!!

Maybe I am missing the Main point of this article BUT, We (humans) share 40%of our D N A with Bananas.TheÂ research associatingÂ the rice gene is negligible compared to what we already KNOW! of ,naturally grown, rice's many positive benefits . P S daruma doll is a Monsanto Hugging SuitÂ exposed by Â Tree Hugger xntrek.Â thanksÂ man!!

"Discover how what we eat can extend our age"... can extrapolate toÂ if we don't eat food, we die.Â So the longer we eat, the longer we live.Â I'd like to get that research grant.Â The work of limiting caloric intake and replacing functional calories with non-nutritive calories is currently widespread in the USA, with millions of participants in the study...

"Discover how what we eat can extend our age"... can extrapolate toÂ if we don't eat food, we die.Â So the longer we eat, the longer we live.Â I'd like to get that research grant.Â The work of limiting caloric intake and replacing functional calories with non-nutritive calories is currently widespread in the USA, with millions of participants in the study...

Agreed. During my life, most things this flabbergasting have turned out to be wrong. Let's see it tested in some lab that does not have miR168 contaminating every surface. If true, it's a game changer for many areas of science and medicine, so I hope it is true. But it seems too dramatically inconsistent with the nature of RNA, 3' methyl or not. Put it to the test.

Agreed. During my life, most things this flabbergasting have turned out to be wrong. Let's see it tested in some lab that does not have miR168 contaminating every surface. If true, it's a game changer for many areas of science and medicine, so I hope it is true. But it seems too dramatically inconsistent with the nature of RNA, 3' methyl or not. Put it to the test.

This fascinating news corroborates Pellionisz's Recursive Genome Function, as earlier demonstrated, from the clinical view-point, by well-known Manuel's Story, the first newborn without predisposition to cancer although its mother was positive before therapy.

This fascinating news corroborates Pellionisz's Recursive Genome Function, as earlier demonstrated, from the clinical view-point, by well-known Manuel's Story, the first newborn without predisposition to cancer although its mother was positive before therapy.